Complications of White-coat Hypertension Compared to a Normotensive and Hypertensive Population.

BACKGROUND: Accumulating evidence demonstrates that white-coat hypertension (WCH) are associated with several risks and complications. In this study, we aimed to investigate the adverse effects of WCH compared with hypertensive and normotensive patients.
METHODS: A retrospective cohort study was conducted over five years. Blood pressure (BP) data was collected from both clinic visits and 24-h ambulatory blood pressure monitoring (ABPM) reports. Epidemiological data and complications, cardiac and noncardiac, were also recorded.
RESULTS: In total, 286 participants who were followed up for at least three years were included. The sample was divided into 99 normotensive patients (as a control group), 94 patients with clinically diagnosed hypertension (HTN), and 93 patients with WCH. Ischemic heart disease (IHD) was the most noted complication in the WCH group with a relative risk of 9.58 (1.23-74.16) (P = 0.008). Acute coronary syndrome (ACS) was significantly correlated with a relative risk of 2.06 (0.52-13.38). No significant correlation was noted with noncardiac complications. Both HTN and WCH groups showed a significant association with blood pressure variability (BPV). WCH was associated with an increased BPV in ambulatory daytime systolic measurements (P = 0.031) and a unique increase in diastolic measurement variability in office BP measurements (P = 0.020).
CONCLUSION: WCH should be managed as HTN. WCH is associated with cardiac complications, particularly IHD, specifically in patients 55 years and older. WCH was significantly associated with a higher BPV in both ABPM and office-based measurements. Copyright:

INTRODUCTION

White-coat hypertension (WCH) is defined as clinic blood pressure (BP) measurements with an average above 130/80 mmHg with reliable out-of-office measurements averaging less than 130/80 mmHg. WCH is a frequent source of misdiagnosis of hypertension (HTN).

According to the World Health Organization (WHO), the prevalence of WCH in the overall population is 33%.[1] The same study reported that the prevalence in individuals with borderline hypertension and the group being assessed for antihypertensive medication was 32.8% and 37%, respectively.[1] In developing countries such as Saudi Arabia, the prevalence of WCH is 48%.[2]

Growing evidence demonstrates that WCH is associated with various risks and complications.[34] Patients with WCH are more likely to develop sustained hypertension, dyslipidemia, and end-organ damage in future.[4] Patients with WCH are at an increased risk of mortality from cardiovascular events and more likely to experience cardiovascular events compared to normotensive patients.[5] Other complications include changes in the mass of the left ventricle, the size of the left atria, preclinical renal damage, and elevated cystatin-c levels.[4]

There is an increasing controversy regarding the complications of WCH compared with the HTN and normotensive groups. In addition, only a few studies investigated the effect of blood pressure variability (BPV) in WCH patients compared to HTN and normotensive groups.

METHODOLOGY

This study is a retrospective cohort study performed at a public hospital in Jeddah, Saudi Arabia. The electronic records of patients, attending the cardiology clinics over a period of 5 years, were included. The eligible records were reviewed, and the data were collected over a year. BP data were collected from both the clinic visit and 24-h ABPM report.

All patients included were older than 18 years at the time of the HTN diagnosis, with at least one ABPM report and at least three recorded BP measurements. Patients with a follow-up time less than 3 years were excluded. We used consecutive sampling, a nonprobability sampling technique.

Multiple variables were collected for each patient based on the interviews and physical examination during the consultation. These include age, gender, weight, height, body mass index (BMI), known cardiovascular risk factors, such as smoking, diabetes mellitus, and dyslipidemia. The complications were divided in cardiac and non-cardiac complications. Cardiac complications included ACS, IHD, heart failure (HF) and left ventricular hypertrophy and vascular noncardiac complications, stroke, and renal failure.

The sample was grouped in three categories based on the BP measurements: Control group, defined on the basis of office measurements of BP <140/90 mmHg and ABPM daytime BP <135/85 mmHg; HTN group defined as patients with an increased office measurement of BP ≥140/90 mmHg for three readings in different visits AND an ABPM daytime BP ≥135/85 mmHg. Lastly, the WCH group included patients with office measurements of BP ≥140/90 mmHg for three readings in different visits AND an ABPM daytime BP <135/85 mmHg.

Data are presented as proportions for qualitative variables and as mean ± SD for quantitative variables. The data related to the complications were analyzed using a Pearson χ2 or a Fischer Exact test. Relative risks (RR) were calculated for each complication with a confidence interval (CI) of 95%.

The association between the groups and the BPV of both office visits and ABPM were analyzed using a binary logistic regression One-Way ANOVA: post hoc Dunnett analysis. The differences between the means of each parameter were also calculated with a CI of 95%.

Ethical approval was granted by the Ministry of Health in Saudi Arabia, Medical Research and Studies Department. An informed consent was not required as the study was a retrospective chart review and no patient identifiers were collected. All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS, as per IRB) version 20.

RESULTS

The sample size realized as 286 participants. The mean age of the control group (n = 99), HTN group (n = 94), and WCH group (n = 93) was 51.8 ± 14.8, 56.5 ± 13.7 and 48.8 ± 14.0 years, respectively. The proportion of males in the three groups was for the control group (45.5%), HTN group (56.5%), and WCH group (48.9%). The prevalence of smoking and dyslipidemia was almost similar in all groups. The obesity and diabetes mellitus proportions were higher in the HTN group (56.4%). Dyslipidemia was also more prevalent in the WCH and HTN groups, respectively, (34.4, 33.0%) but not statistically significant [Table 1]. The duration of follow-up was almost similar between the three groups (5.3 ± 3.0 years).

Table 1

Baseline characteristic of sample (n=286)

Characteristic	Control (n=99)	HTN (n=94)	WCH (n=93)
Age	51.8±14.8	56.5±13.7	48.8±14.0
Male, n (%)	47 (47.5)	50 (53.2)	47 (50.5)
Obesity, n (%)	11 (11.1)	21 (22.3)	12 (12.9)
Smoking, n (%)	9 (9.1)	9 (9.6)	8 (8.6)
Dyslipidemia, n (%)	26 (26.3)	31 (33.0)	32 (34.4)
Diabetes, n (%)	43 (43.4)	53 (56.4)	37 (39.8)
Previous cardiac events, n (%)
Acute coronary syndrome	14 (14.1)	5 (5.3)	5 (5.4)
Chronic ischemic heart disease	20 (20.2)	23 (24.5)	13 (14.0)
Heart failure	4 (4.0)	5 (5.3)	0
Overall cardiac events	30 (30.3)	28 (29.8)	15 (16.1)
Previous noncardiac events, n (%)
Stroke	1 (1.0)	4 (4.3)	2 (2.2)
Renal failure	1 (1.0)	4 (4.3)	1 (1.1)
Overall noncardiac events	2 (2.0)	8 (8.5)	3 (3.2)
Overall previous events, n (%)	31 (31.3)	34 (36.2)	16 (17.2)
Follow-up duration	5.3±3.0	4.8±2.9	5.2±2.7
Developed cardiac complications, n (%)
Acute coronary syndrome	2 (2.0)	9 (9.6)	5 (5.4)
Chronic ischemic heart disease	1 (1.0)	4 (4.3)	9 (9.7)
Heart failure	2 (2.0)	8 (8.5)	0
Overall cardiac complications	4 (4.0)	20 (21.3)	12 (12.9)
Developed noncardiac complications, n (%)
Stroke	1 (1.0)	6 (6.4)	2 (2.2)
Renal failure	0	1 (1.1)	0
Overall noncardiac complications	1 (1.0)	7 (7.4)	2 (2.2)
Overall developed complications	4 (4.0)	26 (27.7)	13 (14.0)
Ambulatory BP variability measurements
SD systolic BP 24 h	13.2±4.1	15.1±5.1	14.3±4.4
SD systolic BP daytime	12.4±4.3	13.9±4.4	14.0±4.5
SD systolic BP night	10.3±4.5	13.3±7.2	10.7±6.2
SD diastolic BP 24 h	10.4±3.3	11.4±3.9	11.2±3.3
SD diastolic BP daytime	9.7±3.3	10.6±3.9	10.9±3.3
SD diastolic BP night	8.4±3.6	9.9±4.6	9.1±4.7
Office BP measurements (mean of at least 3 visits)
SD systolic BP	17.2±9.4	20.2±11.0	20.2±11.7
SD diastolic BP	8.6±6.3	9.6±5.5	11.4±8.6

HTN: Hypertensive group, WCH: White-coat hypertensive group, SD: Standard deviation, BP: Blood pressure

The WCH group had significant cardiac complications but was not significant for stroke or renal failure. The combined cardiac complications were less frequent compared to the HTN group, but IHD occurred more frequently in the WCH group, with a RR of 9.58 (1.23–74.16, P = 0.008) [Table 2].

Table 2

Developed complications correlating with both the groups compared to the control group, Pearson Chi-square or Fisher’s exact test are used in this analysis

Complication	P (RR; 95% CI)
	HTN	WCH
Developed cardiac complications
Acute coronary syndrome	0.024 (4.73; 1.05-21.36)	0.267 (2.06; 0.52-13.38)
Chronic ischemic heart disease	0.202 (4.21; 0.48-37.00)	0.008 (9.58; 1.23-74.16)
Heart failure	0.053 (4.21; 0.91-19.33)	NA
Left ventricular hypertrophy	0.111 (5.266; 0.62-44.24)	1.000 (1.060; 0.68-16.77)
Overall cardiac complications	<0.001 (5.26; 1.86-14.83)	0.026 (3.19; 1.06-9.55)
Developed non cardiac complications
Stroke	0.060 (6.31; 0.77-51.50)	0.612 (2.12; 0.19-23.15)
Renal failure	NA	NA
Overall noncardiac complications	0.031 (7.37; 0.92-58.78)	0.612 (2.12; 0.19-23.09)
Overall complications	<0.001 (6.84; 2.48-18.87)	0.015 (3.46; 1.17-10.23)

RR: Relative risk, CI: Confidence interval, NA: Not applicable, HTN: Hypertensive group, WCH: White-coat hypertensive group

As can be expected, the HTN group had higher proportions of cardiac complications, stroke, and renal failure. ACS had an RR of 4.73 (1.05–21.36, P = 0.024). However, the development of stroke and renal failure was 7.37 (0.92–58.78, P = 0.031), [Figure 1].

Figure 1

A bar chart showing the percentage of developed complications (as cardiac, noncardiac, or both) in all groups: hypertensive group and white-coat hypertensive group

ACS was associated with WCH and HTN groups with a RR of 2.06 (0.52–13.38), but there was no statistically significant difference between WCH and HTN (P = 0.267). A subgroup analysis of the age of the WCH group indicated that cardiac complications were significant in the group older than 55 years compared to an age-matched normotensive group (P = 0.018) and RR: 8.96 (1.16–69.22) [Table 3].

Table 3

Dividing the white-coat hypertensive group into two subgroups based on age and correlating the subgroups with the developed complications

Complication	WCH, P (RR; 95% CI)
	Age <55 (n=61)	Age ≥55 (n=32)	All ages (n=93)
Overall cardiac complications	0.718 (1.58; 0.396-6.33)	0.018 (8.96; 1.16-69.22)	0.026 (3.19; 1.06-9.55)
Overall noncardiac complications	NA	0.688 (1.28; 0.08-19.70)	0.612 (2.12; 0.19-23.09)
Overall complications	0.718 (1.58; 0.396-6.33)	0.008 (10.25; 1.35-77.79)	0.015 (3.46; 1.17-10.23)

RR: Relative risk, CI: Confidence interval, NA: Not applicable, WCH: White-coat hypertensive group

BPV was associated with a poor outcome. Both the HTN and WCH groups had a significant association with BPV. In the HTN group, the most notable measurements were the variability of the BP at night (P = 0.001) and a variability of the systolic BP of the 24 h monitoring (P = 0.007). The WCH group indicated variability in the SD of the BP in the daytime measurements (P = 0.031). Interestingly, we also noted increased variability in the office BP measurements, the SD of the systolic BP of at least three visits was statistically significant (P = 0.020) [Table 4].

Table 4

The association between blood pressure variability (measure by ambulatory blood pressure measurement device or office setting) and both groups in comparison to the control group, one-way ANOVA and Post hoc Dunnett analysis are used

BPV parameter	P (mean difference; 95% CI)
	HTN	WCH
Ambulatory BP variability measurements
SD systolic BP 24 h	0.007 (1.92; 0.46-3.38)	0.181 (1.07; −0.38-2.53)
SD systolic BP daytime	0.035 (1.49; 0.08-2.90)	0.031 (1.53; 0.12-2.94)
SD systolic BP night	0.001 (2.99; 1.06-4.93)	0.893 (0.34; −1.59-2.28)
SD diastolic BP 24 h	0.075 (1.03; −0.08-2.16)	0.171 (0.84; −0.28-1.97)
SD diastolic BP daytime	0.122 (0.93; −0.20-2.06)	0.032 (1.22; 0.08-2.36)
SD diastolic BP night	0.032 (1.48; 0.11-2.86)	0.445 (0.67; −0.70-2.06)
Office BP measurements
SD systolic BP	0.103 (2.95; −0.47-6.39)	0.100 (2.98; −0.46-6.42)
SD diastolic BP	0.345 (0.78; −1.42-2.99)	0.020 (2.56; 0.35-4.77)

BP: Blood pressure, BPV: BP variability, HTN: Hypertensive group, WCH: Whit-coat hypertensive group, CI: Confidence interval, SD: Standard deviation

DISCUSSION

Based on the current results, WCH is not a benign disease. Cardiac complications were only slightly less than in the HTN group. It should be noted that the WCH group was associated with significant BPV during daytime and in office visits. The prognosis of WCH was worse in the group older than 55 years.

In literature, the relationship between WCH and complications is still controversial. In a recent systematic review and meta-analysis, WCH patients were more likely to have cardiovascular disease or sustained HTN in future, but it was not associated with stroke or all-cause mortality.[56] Some studies consider WCH as HTN in terms of prognosis and the effect of WCH on end-organ damage.[7] It was postulated that with aging and an increase in the arterial stiffness of the vessels, the frequency of WCH increases.[3] Baroreceptor sensitivity declines with aging, causing larger fluctuations in BP measurement with psychological stress such as being at the doctor's office.[58]

It is important to identify patients with WCH as they require intensive risk factor modification, closer monitoring of their office and home BP measurements, and more frequent assessment with ambulatory BP monitoring to identify the conversion to sustained HTN and reduce their risk of developing complications.[49] In particular, WCH patients, with considerable variation in BP, are prone to a high cardiovascular risk and need special attention.

The association of the age of WCH patients with the development of complications is also controversial.[1011] In the current study, the subgroup analysis revealed that the cardiac complications were more significant in the group older than 55 years compared to their age-matched normotensive group. In addition, WCH was highly associated with developing IHD, in contrast to other studies suggesting associations with cardiovascular death, coronary heart disease, stroke, HF, and atrial fibrillation.[12] WCH had BPV in both the ABPM and office measurements, which is not widely discussed in literature. Patients with a high BPV are at an increased risk of developing cardiac and noncardiac complications compared to low BPV.[1314]

A recent study using SPRINT data, demonstrated that higher BPV is associated with increased adverse events and that the coefficients of variation of diastolic blood pressure predicted an increased risk of cardiovascular comorbidities and mortality.[15]

CONCLUSION

Patients with WCH had a statistically significant risk to develop IHD, in addition to all other complications, especially in the group older than 55 years. WCH was also associated with increased variability in both ambulatory daytime systolic BP and office diastolic BP measurements.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.